IFN-γ Approaches in Tumor Suppression, Its Challenges, and Future Directions: A Review of Recent Advances

IFN-γ is recognized as an immunoregulatory cytokine due to its dual role in both accelerating and dampening immunological responses. Accordingly, in the context of tumor immunotherapy, the therapeutic outcome of IFN-γ is contingent upon factors such as dosage and the expression status of downstream signaling molecules. Furthermore, the coadministration of IFN-γ with various immunestimulatory agents, including anticheckpoint inhibitors, chemotherapeutic agents, and herbal-based medicines, may potentially overcome the IFN-γ-related challenges and enhance the response rate. We decipher the mechanisms of tumor cell eradication facilitated by IFN-γ, the last achievements in IFN-γ-mediated tumor immunotherapy across various cancers, and the strategies to address the failure of IFN-γ-based tumor immunotherapy. Unraveling the molecular mechanisms that lead to failure in IFN-γ-based antitumor actions could assist in pinpointing therapeutic agents that target the immune-modulatory features of IFN-γ, thereby increasing the antitumor response rate.